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About centuries after the communique by way of Sir Percival Pott that the "chimney sweeper illness" was once a melanoma and its advice that energetic compounds of soot have been the causative brokers, and approximately one century after the outline of urinary bladder melanoma in dye employees, a tremendous variety of elements were synthesized and feature most likely come into touch with guy. learn in melanoma prevention is of basic value, and will obtain non-stop aid from new discoveries on melanoma etiology and pathogenesis. If one accepts the multistage version of chemical carcinogenesis, one has additionally to just accept that many occasions ensue among the touch of carcino genic compounds and their particular objectives and the advance of a clinically recognizable neoplasm. hence, animal experiences develop into necessary to elucidate the several steps wherein chemical cancer agents result in neoplasia. The research of those steps and the comparative overview of experimental versions is vital to an knowing of pathogenesis.
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Extra resources for Chemical Carcinogenesis: Models and Mechanisms
Pal and A. Hewer, Metabolic activation of benzo(a)pyrene proceeds by a diol-epoxide, Nature 252:326 (1974). M. D. Buening, P. G. Wislocki, W. Levin, H. Yagi, D. R. Thakker, H. Akagi, M. Koreeda, D. M. Jerina and A. H. Conney, Tumorigenicity of the optical enantiomers of the diastereomeric benzo(a)pyrene-7,8-diol-9,10-epoxide in newborn mice: Exceptional activity of (+)-7B,8u-dihydroxy-9u,IOu-epoxy-7,8,9,10-tetrahydrobenzo(a)pyrene, Proc. Natl. Acad. Sci. USA 75:5358 (1978). T. J. Slaga, W. J. Bracken, G.
Hepatic ring-oxidation, an important detoxification pathway for these arylamines, also varied greatly between the substrates with ring-oxidation representing >60% of total metabolism for 2-NA, <2% for ABP, and 14-80% with MOCA with different isozymes 15 - 17 • Human hepatic microsomal preparations from different individuals have Table 1. 62 a'Taken from ref. lS; btaken from refs. 16 and 17; Ctaken from ref. 18. 18 been shown to vary considerably in their oxidative ability to activate (N-oxidation) and detoxify (ring-oxidation) several aromatic amines of significant potential human exposure (Table 2).
A. Beland and F. F. Kadlubar, Metabolic activation of carcinogenic arylamines by rat, dog and human hepatic microsomes and by purified flavin-containing and cytochrome P-450 monooxygenases, Cancer Res. 45:3578 (1985). F. Kadlubar, M. A. Butler, B. W. Hayes, F. A. Beland and F. P. Guengerich, Role of microsomal cytochrome P-450 and prostaglandin H synthase in 4-aminobiphenyl-DNA adduct formation, in: "Microsomes and Drug Oxidation", D. W. , Taylor and Francis, London, in press. P. Guengerich, M.